As a recent graduate from a PhD program and newly appointed assistant professor at The University of Iowa, I feel that I would benefit significantly from the Faculty Transition portion of the K22. In conjunction with the completion of the research proposed, the PI will receive training in the ethics of biomedical research. The research project itself will receive guidance from a number of very experienced researchers. Drs. Michael Pfaller, Christopher Squier, Georgia Johnson, Philip Wertz and David Soll. The research experience that is outlined in this proposal will enable me to develop into an independent investigator and contributor to the advancement of science. I will receive extensive support from my advisors and the College of Dentistry. Research facilities are available for my use and courses are offered that will enable me to conduct research in a responsible manner. The. experimental portion sets out to answer the following questions: 1. What is the antifungal susceptibility of C. albicans switch phenotypes isolated from HIV-positive individuals? 2. Are there differences in uptake of antifungals among different switch phenotypes or differences in ergosterol content in the presence of antifungals and are there differences in expression of known multi-drug resistance genes (MDR1, CDR1 and ERG11) among the different switch phenotypes? and 3. Are different switch phenotypes better able to survive under in vivo conditions of antifungal drug therapy for candidiasis? For this, a collection of samples from HIV+ and HIV- individuals previously collected by the PI and Dr. Michael Pfaller will be used. From these studies we hope to increase our understanding of the role that phenotypic switching plays in antifungal drug resistance, which is an increasing problem in severely immunosuppressed individuals. This increased knowledge could lead to improvements in treatment of oral candidiasis in all immunocompromised individuals. In the long-term, I would like to make significant contributions to science in the area of antifungal drug resistance. It is an exciting area of research and I feel strongly that I have the motivation to accomplish this goal.